Coronary artery disease (CAD) leads to the highest mortality worldwide, seriously threatening human health. Tanshinone IIA (Tan IIA), which could be extracted from Danshen, is applied in the treatment of cardiovascular and cerebrovascular diseases. MicroRNAs (miRNAs, miRs) play pivotal roles in cell proliferation and cell apoptosis of the cardiovascular system. The aim of the present study was to explore the role of Tan IIA in CAD in vitro and the underlying molecular mechanism.
Real-time polymerase chain reaction (RT-PCR) and Western blot were used for the detection of miRNA/mRNA and protein, respectively. Target genes of miR-133a-3p were searched in TargetScan, and the targeting relationship was verified by dual-luciferase reporter assay. Cell proliferation was determined using a Cell Counting Kit-8 (CCK-8) and EdU labeling. Cell apoptosis was detected by flow cytometry and TUNEL staining.
In the present study, lower miR-133a-3p level and higher epidermal growth factor receptor (EGFR; the target of miR-133a-3p) level were found in HO-induced H9c2 cells. In addition, Tan IIA upregulated miR-133a-3p and downregulated EGFR expression. Moreover, Tan IIA promoted cell proliferation and suppressed apoptosis and enhanced G0/G1, which was reversed by miR-133a-3p inhibitor, while siRNA-EGFR abolished the effects induced by miR-133a-3p in HO-induced H9c2 cells.
Tan IIA reversed HO-induced cell proliferation reduction, cell apoptosis induction, and G0/G1 arrest reduction in H9c2 cells by miR-133a-3p/EGFR axis. The findings suggested a potential molecular basis of Tan IIA in treating patients with CAD.
Tan IIA reversed H2O2-induced cell proliferation reduction, cell apoptosis induction, and G0/G1 arrest reduction in H9c2 cells by miR-133a-3p/EGFR axis. The findings suggested a potential molecular basis of Tan IIA in treating patients with CAD.The present study was designed to evaluate the anti-inflammatory effects of different doses of aliskiren in two animal models of inflammation.
Sixty-six Wistar rats were allocated into five groups the first group (six rats) was treated with the vehicle only, without induction of paw edema and granulomatous inflammation, and served as a negative control; the second group (12 rats) was allocated into two subgroups and treated with the vehicle only, with induction of paw edema and granulomatous inflammation, and served as a positive control; the third group (36 rats) was allocated into six subgroups and treated with different doses of aliskiren (15, 30, and 60 mg/kg) in both models; the fourth group (12 rats) was treated with dexamethasone (1 mg/kg) in both models of inflammation. Serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), vascular cell adhesion molecule-1 (VCAM-1), and high sensitivity C-reactive protein (hs-CRP) were measured. Skin samples were also sent for histopathological examination.
Aliskiren, in a dose-dependent pattern, significantly decreased inflammation in rat models of inflammation, by attenuating the percentage of exudate, granuloma, and paw edema. Furthermore, it significantly reduced serum concentrations of TNF-α, VCAM-1, and hs-CRP and restored the serum concentration of IL-10. Additionally, significant improvement was seen in the histopathological findings.
In the current study, aliskiren was successful in decreasing inflammation in both models. These findings suggest that aliskiren is a good candidate for the treatment of inflammatory diseases.
In the current study, aliskiren was successful in decreasing inflammation in both models. These findings suggest that aliskiren is a good candidate for the treatment of inflammatory diseases.We evaluated the appropriateness of various equivalence margins for CT-P13, an infliximab biosimilar, in the PLANETRA clinical trial. The 95-95% method was used to independently determine an equivalence margin by pooling the historical clinical trials with original infliximab versus placebo, identified in a systematic literature search. The constancy assumption with the PLANETRA trial was assessed for each identified historical clinical trial to decide which study was scientifically justifiable to be pooled. A sensitivity analysis was performed for each study-pooling scenario. As a result, we identified two historical clinical trials that were deemed appropriate, whereas the PLANETRA trial pooled three additional studies to determine an equivalence margin, which was accepted by the United States Food and Drug Administration. However, those extra clinical trials did not meet the constancy assumption in baseline characteristics, methotrexate dose, and efficacy assessment time. The clinically more appropriate equivalence margin was 5.7 percentage points, which was much narrower than the 12 percentage points applied in the approval of CT-P13. In conclusion, the equivalence claim for CT-P13 to original infliximab in patients with rheumatoid arthritis did not appear to be supported when the constancy assumption was strictly assessed. https://www.selleckchem.com/products/cerivastatin-sodium.html The equivalence margin for biosimilars could be determined more conservatively.Chondrocyte-mediated inflammation is an important pathological component of osteoarthritis (OA) development. There are currently no therapies that completely reverse the development of OA. Lentinan, a type of polysaccharide derived from Lentinus edodes, has been demonstrated to possess significant anti-viral, anti-cancer, and anti-inflammatory effects, and has been recently used in the treatment of several inflammatory diseases. However, little research has focused on the pharmacological effect of lentinan in human OA.
We evaluated the anti-inflammatory and anti-ROS effects of lentinan in SW1353 chondrocytes treated with AGEs using real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and the nitro oxide-specific stain DAF-FM DA. The regulatory effects of lentinan on NF-κB and MAPK p38 signaling were investigated via promoter assay and Western blot analysis.
We found that lentinan inhibits the production of pro-inflammatory cytokines, including IL-1β, TNF-α, IL-8 and the secretion of PGEand NO, by reducing the expression of COX-2 and iNOS in AGE-challenged chondrocytes.